Rubrics defining a signaling microdomain

In this review, at least two rules listed below are required to consider a group of proteins as part of a signaling microdomain that can regulate cellular communication. Examples of signaling microdomain applicable to each guideline are indicated in the right column.

1. Proteins are concentrated to a region of the cell (i.e., apical membrane, myoendothelial junction) and altogether participate in a specific cellular function.Exocytosis at the apical membrane (section IV)
Endothelium-dependent hyperpolarization-mediated response (section III.C)
2. There is an accumulation of two or more proteins contained within a membranous phospholipid region (i.e., lipid raft, caveolae), and the loss of this structure alters cell-cell communication.eNOS localized in caveolae (section II.A)
3. There is a direct protein-protein interaction, and disruption of this interaction alters cell-cell communication.eNOS and caveolin 1 (section II.A.1)
eNOS and Hbα (section II.A.4)
Cx43 and ZO-1 (section III.A.4)
4. There is evidence for close localization of proteins, with a loss of one of the proteins (function or expression) altering the way in which cell-cell communication occurs.Endothelium-dependent hyperpolarization-mediated response (section III.A)